Impact of Lipidic Plaque on In-Stent and Stent Edge-Related Events After PCI in Myocardial Infarction: A PROSPECT II Substudy.

BACKGROUND: Lipid content in untreated nonobstructive coronary artery lesions is associated with adverse clinical outcomes, and residual in-stent or stent edge lipid may worsen outcomes after percutaneous coronary intervention (PCI). METHODS: Near-infrared spectroscopy-intravascular ultrasound was performed before and after PCI in patients with myocardial infarction. We evaluated the impact of lipid assessed by near-infrared spectroscopy (maximal lipid core burden index over 4 mm [maxLCBI4mm]) along with intravascular ultrasound information including residual plaque burden on in-stent or edge-related major adverse cardiac events (MACE) in de novo PCI-treated culprit coronary artery lesions. The primary end point was culprit lesion-related MACE (CL-MACE), defined as cardiac death, myocardial infarction, or unstable or progressive angina either requiring revascularization or with rapid lesion progression and classified as in-stent or stent edge-related. RESULTS: During a median follow-up of 3.8 years, 25 CL-MACE (11 stent edge-related, 13 in-stent, and 1 in-lesion without a stent) occurred in 1041 PCI-treated lesions in 768 patients. Pre-PCI or post-PCI measures of lipid content were not related to in-stent CL-MACE. However, stent edge-related CL-MACE was increased if both the post-PCI stent edge maxLCBI4mm was greater than the upper quartile (108.7) and the stent edge plaque burden was >50% (adjusted odds ratio, 4.11 [95% CI, 1.12-15.2]; P=0.03). CONCLUSIONS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), CL stent implantation leaving behind greater stent edge-related lipid and uncovered plaque burden was associated with an increased risk of stent edge-related CL-MACE during follow-up. In contrast, CL lipid content was not related to in-stent CL-MACE. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02171065.

Complete vs. Culprit-Only Revascularization in Older Patients with ST-segment Elevation Myocardial Infarction: An Individual Patient Meta-Analysis.

Background: Complete revascularization is the standard treatment for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit ( > 1-year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in STEMI patients aged 75 years or older enrolled in randomized clinical trials investigating complete vs. culprit-only revascularization strategies. Methods: PubMed, Embase, and the Cochrane database, were systematically searched to identify randomized clinical trials comparing complete vs. culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary endpoint was death, myocardial infarction (MI), or ischemia-driven revascularization. The secondary endpoint was cardiovascular death or myocardial infarction. Results: Data from seven RCTs, encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization), were analyzed. The median age was 79 [77-83] years. Females were 595 (34%). Follow-up ranged from a minimum of six months to a maximum of 6.2 years (median 2.5 [1-3.8] years). Complete revascularization reduced the primary endpoint up to four years (HR 0.78, 95%CI 0.63-0.96), but not at the longest available follow-up (HR 0.83, 95%CI 0.69-1.01). Complete revascularization significantly reduced the occurrence of cardiovascular death or MI at the longest available follow-up (HR 0.76, 95%CI 0.58-0.99). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. Conclusions: In this individual patient data meta-analysis of older STEMI patients with multivessel disease, complete revascularization reduced the primary endpoint of death, MI or ischemia-driven revascularization up to 4-year. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or MI, but not the primary endpoint. Clinical Study Registration: PROSPERO CRD42022367898.

Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial.

Importance: Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach). Objective: To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events. Design, Setting, and Participants: The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023. Interventions: Alirocumab or placebo in addition to high-intensity statin therapy. Main Outcomes and Measures: Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes. Results: Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02). Conclusions and Relevance: At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

BACKGROUND: The benefit of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease and severe aortic stenosis who are undergoing transcatheter aortic-valve implantation (TAVI) remains unclear. METHODS: In an international trial, we randomly assigned, in a 1:1 ratio, patients with severe symptomatic aortic stenosis and at least one coronary-artery stenosis with a fractional flow reserve of 0.80 or less or a diameter stenosis of at least 90% either to undergo PCI or to receive conservative treatment, with all patients also undergoing TAVI. The primary end point was a major adverse cardiac event, defined as a composite of death from any cause, myocardial infarction, or urgent revascularization. Safety, including bleeding events and procedural complications, was assessed. RESULTS: A total of 455 patients underwent randomization: 227 to the PCI group and 228 to the conservative-treatment group. The median age of the patients was 82 years (interquartile range, 78 to 85), and the median Society of Thoracic Surgeons-Procedural Risk of Mortality score (on a scale from 0 to 100%, with higher scores indicating a greater risk of death within 30 days after the procedure) was 3% (interquartile range, 2 to 4). At a median follow-up of 2 years (interquartile range, 1 to 4), a major adverse cardiac event (primary end point) had occurred in 60 patients (26%) in the PCI group and in 81 (36%) in the conservative-treatment group (hazard ratio, 0.71; 95% confidence interval [CI], 0.51 to 0.99; P = 0.04). A bleeding event occurred in 64 patients (28%) in the PCI group and in 45 (20%) in the conservative-treatment group (hazard ratio, 1.51; 95% CI, 1.03 to 2.22). In the PCI group, 7 patients (3%) had PCI procedure-related complications. CONCLUSIONS: Among patients with coronary artery disease who were undergoing TAVI, PCI was associated with a lower risk of a composite of death from any cause, myocardial infarction, or urgent revascularization at a median follow-up of 2 years than conservative treatment. (Funded by Boston Scientific and the Danish Heart Foundation; NOTION-3 ClinicalTrials.gov number, NCT03058627.).

Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial.

Importance: In patients with ST-segment elevation myocardial infarction (STEMI), acute inflammation is related to the extent of myocardial damage and may increase infarct size. Thus, administration of pulse-dose glucocorticoid in the very early phase of infarction may reduce infarct size. Objective: To determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI. Design, Setting, and Participants: This was a 1:1 investigator-initiated, blinded, placebo-controlled, randomized clinical trial conducted between November 14, 2022, and October 17, 2023, with last follow-up on January 17, 2024. Patients 18 years and older with less than 12 hours of acute chest pain and STEMI were included in the prehospital setting throughout the Region Zealand and Capital Region of Denmark and transferred to Rigshospitalet, Denmark. Intervention: Patients were randomly allocated to intravenous glucocorticoid (methylprednisolone, 250 mg) or placebo in the prehospital setting. Main Outcomes and Measures: The primary outcome was final infarct size on cardiac magnetic resonance (CMR) at 3 months. The power calculation was based on an anticipated final infarct size of 13%. Secondary outcomes included CMR outcomes on acute scan and at 3 months, peak of cardiac biomarkers, clinical end points at 3 months, and adverse events. Results: Of 530 included patients (median [IQR] age, 65 [56-75] years; 418 male [78.9%]) with STEMI, 401 (76%) were assessed for the primary outcome, with 198 patients treated with glucocorticoid and 203 with placebo. Median final infarct size was similar in the treatment groups (glucocorticoid, 5%; IQR, 2%-11% vs placebo, 6%; IQR, 2%-13%; P = .24). Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78; 95% CI, 0.61-1.00), less microvascular obstruction (relative risk ratio, 0.83; 95% CI, 0.71-0.99), and greater acute left ventricular ejection fraction (mean difference, 4.44%; 95% CI, 2.01%-6.87%). Other secondary outcomes were similar in both groups. Conclusions and Relevance: In patients with STEMI, treatment with prehospital pulse-dose glucocorticoid did not reduce final infarct size after 3 months. However, the trial was likely underpowered as the final infarct size was smaller than anticipated. The glucocorticoid group had improved acute parameters compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05462730.

Time From Distress Call to Percutaneous Coronary Intervention and Outcomes in Myocardial Infarction.

Background: Early percutaneous coronary intervention (PCI) is recommended for ST-segment elevation myocardial infarction (STEMI) treatment. Delays in time-to-PCI, kept within guideline recommendations, have seldom been investigated. Objectives: The purpose of this study was to investigate the consequences of delay, due to system factors or hospital distance, for the time between last patient distress call and PCI. Methods: Registry-based cohort study including times of first call to medical services, admission and PCI for patients admitted with STEMI in Copenhagen, Denmark (2014-2018). The main combined outcome included death, recurrent myocardial infarction, or heart failure estimated at 30 days and 1 year from event. Outcomes according to time from call to PCI (system delay) and door-to-balloon time were standardized to the STEMI population using multivariate logistic regression. Results: In total, 1,822 STEMI patients (73.5% male, median age 63.3 years [Q1-Q3: 54.6-72.9 years]) called the emergency services ≤72 hours before PCI (1,735, ≤12 hours). The combined endpoint of 1-year cumulative incidence was 13.9% (166/1,196) for patients treated within 120 minutes of the call and 21.2% (89/420) for patients treated later. Standardized 30-day outcomes were 7.33% (95% CI: 5.41%-9.63%) for patients treated <60 minutes, and 11.1% (95% CI: 8.39%-14.2%) for patients treated >120 minutes. Conclusions: The risk of recurrent myocardial infarction, death, and heart failure following PCI treatment of STEMI increases rapidly when delay exceeds 1 hour. This indicates a particular advantage of minimizing time from first contact to PCI.

A Systematic Approach to the Evaluation of the Coronary Microcirculation Using Bolus Thermodilution: CATH CMD.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

Familial clustering of unexplained heart failure - A Danish nationwide cohort study.

AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49]. CONCLUSION: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.

Prognostic differences between physiology-guided percutaneous coronary intervention and optimal medical therapy in coronary artery disease: A systematic review and meta-analysis.

Background: Intracoronary physiology, particularly fractional flow reserve (FFR), has been used as a guide for revascularization for patients with coronary artery disease (CAD). The optimal treatment in the physiological grey-zone area has been unclear and remains subject to ongoing debate. Methods: We conducted a systematic review of randomized controlled trials and observational studies comparing the prognostic effect of percutaneous coronary revascularization (PCI) and optimal medical therapy (OMT) in patients with CAD. Studies were identified by medical literature databases. The outcomes of interest were major adverse cardiac events (MACE) and its components, death, myocardial infarction (MI), and repeat revascularization. Results: A total of 16 studies with 27,451 patients were included. The pooled analysis demonstrated that PCI was associated with a prognostic advantage over OMT in patients with FFR value ≤0.80 (RR: 0.64, 95 % CI: 0.45-0.90, p < 0.01). Patients with an FFR value >0.80 were shown to benefit more from OMT (RR 1.38, 95 % CI 1.24-1.53, p < 0.01). The analysis also showed that there was no significant difference in MACE in the grey-zone area (FFR 0.75-0.80) (RR 0.64, 95 % CI: 0.35-1.16, p = 0.14), but a significant reduction in repeat revascularization (RR 0.54, 95 % CI, 0.31-0.91, p < 0.01) when patients were treated with PCI. Conclusions: Among patients with CAD and FFR values >0.80, OMT was associated with favorable outcomes over PCI in reducing the risk of MACE. However, among patients with FFR values ≤0.80, revascularization was superior in terms of reducing MACE. The available evidence supports the guideline-recommended use of an FFR cut-off of ≤0.80.

Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy.

BACKGROUND AND AIMS: The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). METHODS: This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks. RESULTS: 139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62). CONCLUSIONS: Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.

The role of remnant cholesterol in patients with ST-segment elevation myocardial infarction.

AIMS: Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. METHODS AND RESULTS: A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI. CONCLUSION: In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), elevated remnant cholesterol (RC) levels beyond LDL cholesterol were independently associated with increased all-cause mortality.About 38% of patients with STEMI present discordantly high RC, which is associated with elevated all-cause mortality and cardiovascular death.Remnant cholesterol as a continuous variable is associated with higher all-cause mortality.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Prevalence and Impact of Frailty in Patients ≥70 Years Old with Acute Coronary Syndrome Referred for Coronary Angiography.

INTRODUCTION: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). METHODS: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1-3), vulnerable (4), and frail (5-9) and followed for 12 months. RESULTS: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30-5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). CONCLUSIONS: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.